Добірка наукової літератури з теми "Endosomal escape peptide"

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Статті в журналах з теми "Endosomal escape peptide"

1

Nielsen, Peter E. "Addressing the challenges of cellular delivery and bioavailability of peptide nucleic acids (PNA)." Quarterly Reviews of Biophysics 38, no. 4 (November 2005): 345–50. http://dx.doi.org/10.1017/s0033583506004148.

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1. Introduction 3452. Peptide nucleic acid (PNA) 3463. ‘Cell penetrating peptides’ (CPPs) 3464. Endosomal escape 3475. Cellular delivery of PNA 3476.In vivobioavailability of PNA 3497. References 350Recent results on the cellular delivery of antisense peptide nucleic acids (PNA) via peptide conjugation is briefly discussed, in particular in the context of endosomal entrapment and escape.
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2

Bartz, René, Haihong Fan, Jingtao Zhang, Nathalie Innocent, Craig Cherrin, Stephen C. Beck, Yi Pei, et al. "Effective siRNA delivery and target mRNA degradation using an amphipathic peptide to facilitate pH-dependent endosomal escape." Biochemical Journal 435, no. 2 (March 29, 2011): 475–87. http://dx.doi.org/10.1042/bj20101021.

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Effective delivery of siRNA (small interfering RNA) into the cells requires the translocation of siRNA into the cytosol. One potential delivery strategy uses cell-delivery peptides that facilitate this step. In the present paper, we describe the characterization of an amphipathic peptide that mediates the uptake of non-covalently bound siRNA into cells and its subsequent release into the cytosol. Biophysical characterization of peptide and peptide/siRNA mixtures at neutral and lysosomal (acidic) pH suggested the formation of α-helical structure only in endosomes and lysosomes. Surprisingly, even though the peptide enhanced the uptake of siRNA into cells, no direct interaction between siRNA and peptide was observed at neutral pH by isothermal titration calorimetry. Importantly, we show that peptide-mediated siRNA uptake occurred through endocytosis and, by applying novel endosomal-escape assays and cell-fractionation techniques, we demonstrated a pH-dependent alteration in endosome and lysosome integrity and subsequent release of siRNA and other cargo into the cytosol. These results indicate a peptide-mediated siRNA delivery through a pH-dependent and conformation-specific interaction with cellular membranes and not with the cargo.
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Soe, Tet Htut, Kazunori Watanabe, and Takashi Ohtsuki. "Photoinduced Endosomal Escape Mechanism: A View from Photochemical Internalization Mediated by CPP-Photosensitizer Conjugates." Molecules 26, no. 1 (December 23, 2020): 36. http://dx.doi.org/10.3390/molecules26010036.

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Endosomal escape in cell-penetrating peptide (CPP)-based drug/macromolecule delivery systems is frequently insufficient. The CPP-fused molecules tend to remain trapped inside endosomes and end up being degraded rather than delivered into the cytosol. One of the methods for endosomal escape of CPP-fused molecules is photochemical internalization (PCI), which is based on the use of light and a photosensitizer and relies on photoinduced endosomal membrane destabilization to release the cargo molecule. Currently, it remains unclear how this delivery strategy behaves after photostimulation. Recent findings, including our studies using CPP-cargo-photosensitizer conjugates, have shed light on the photoinduced endosomal escape mechanism. In this review, we discuss the structural design of CPP-photosensitizer and CPP-cargo-photosensitizer conjugates, and the PCI mechanism underlying their application.
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Torres, Julián D., Juan C. Cruz, and Luis H. Reyes. "Synthesis, Characterization, and Functionalization of Graphene Oxide-Based Nanoplatforms for Gene Delivery." Materials Proceedings 4, no. 1 (November 11, 2020): 23. http://dx.doi.org/10.3390/iocn2020-07925.

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Gene therapy has been considered a promising strategy for treating several inherited diseases and acquired complex disorders. One crucial challenge yet to be solved to ensure the nanomaterials’ success in delivering gene therapies is their ability to escape from endosomes. To address this issue, we previously developed magnetite nanoparticles conjugated with the antimicrobial peptide Buforin II, which showed potent translocating and endosomal escape abilities in several cell lines. In this work, we propose developing new cell-penetrating nanoplatforms by interfacing graphene oxide (GO) with powerful translocating peptides to take advantage of already tested and unique peptides as well as the distinctive interactions of GO with the phospholipids of membranes and endosomes. GO was prepared by the modified Hummers’ method through the oxidation of graphite sheets. Next, the functionalization of GO was carried out by rendering pendant amine groups to the GO surface. Thermogravimetric analysis (TGA) and Fourier-transform infrared spectroscopy (FTIR) were used to corroborate the successful functionalization of the nanoplatform. FTIR analysis exhibited the peaks related to the distinct carboxyl groups of GO and the Si–O bonds after silanization. TGA allowed us to estimate a silanization efficiency of 38%. Future work will be focused on conjugating Buforin II and assessing translocation efficiency by conducting uptake assays in liposomes and various cell lines. Additionally, endosomal escape will be determined via confocal microscopy by labeling the peptide with fluorescent molecules and examining colocalization with the fluorescent marker of endosomes, LysoTracker. By taking advantage of the exceptional qualities in terms of the physicochemical, electrical, and optical properties of GO, this study might provide novel strategies to overcome limitations commonly faced, such as low stability of the translocating biomolecules and endosomal entrapment.
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Radford, Robert J., Wen Chyan, and Stephen J. Lippard. "Peptide targeting of fluorescein-based sensors to discrete intracellular locales." Chem. Sci. 5, no. 11 (2014): 4512–16. http://dx.doi.org/10.1039/c4sc01280a.

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Анотація:
Fluorescein-labeled peptides are often sequestered within acidic vesicles, diminishing their applicability for live cell imaging. Installing reactive acetyl groups onto the sensing moiety of a labeled peptide facilitates endosomal escape and allows for peptide-based targeting of fluorescent sensors to discrete intracellular locales.
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Shah, Vatsal R., Yamini D. Shah, and Mansi N. Athalye. "Novel approaches in development of cell penetrating peptides." Journal of Applied Pharmaceutical Research 9, no. 1 (March 15, 2021): 1–7. http://dx.doi.org/10.18231/joapr.2021.9.1.08.24.

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Анотація:
Therapeutic cargos which are impermeable to the cell can be delivered by cell penetrating peptides (CPPs). CPP-cargo complexes accumulate by endocytosis inside the cells but they fail to reach the cytosolic space properly as they are often trapped in the endocytic organelles. Here the CPP mediated endosomal escape and some strategies used to increase endosomal escape of CPP-cargo conjugates are discussed with evidence. Potential benefits can be obtained by peptides such as reduction in side effects, biocompatibility, easier synthesis and can be obtained at lower administered doses. The particular peptide known as cell penetrating peptides are able to translocate themselves across membrane with the carrier drugs with different mechanisms. This is of prime importance in drug delivery systems as they have capability to cross physiological membranes. This review describes various mechanisms for effective drug delivery and associated challenges
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Zhang, Qiaoping, Bin Gao, Khan Muhammad, Xubin Zhang, Xiang-kui Ren, Jintang Guo, Shihai Xia, Wencheng Zhang, and Yakai Feng. "Multifunctional gene delivery systems with targeting ligand CAGW and charge reversal function for enhanced angiogenesis." Journal of Materials Chemistry B 7, no. 11 (2019): 1906–19. http://dx.doi.org/10.1039/c8tb03085e.

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Rong, Guangyu, Changping Wang, Lijie Chen, Yang Yan, and Yiyun Cheng. "Fluoroalkylation promotes cytosolic peptide delivery." Science Advances 6, no. 33 (August 2020): eaaz1774. http://dx.doi.org/10.1126/sciadv.aaz1774.

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Анотація:
Cytosolic delivery of peptides remains a challenging task owing to their susceptibility to enzymatic degradation and the existence of multiple intracellular barriers. Here, we report a new strategy to address these issues by decoration of a fluorous tag on the terminal of cargo peptides. The fluorous-tagged peptides were assembled into nanostructures, efficiently internalized by cells via several endocytic pathways and released into the cytosol after endosomal escape. They were relatively stable against enzymatic degradation and showed much higher efficiency than nonfluorinated analogs and cell penetrant peptide–conjugated ones. The proposed strategy also efficiently delivered a proapoptotic peptide into specific sites in the cells and restored the function of cargo peptide after cytosolic delivery. The fluorous-tagged proapoptotic peptide efficiently inhibited tumor growth in vivo. This study provides an efficient fluorination strategy to promote the cytosolic delivery of peptides.
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Mejia, Franklin, Sabrina Khan, David T. Omstead, Christina Minetos, and Basar Bilgicer. "Identification and optimization of tunable endosomal escape parameters for enhanced efficacy in peptide-targeted prodrug-loaded nanoparticles." Nanoscale 14, no. 4 (2022): 1226–40. http://dx.doi.org/10.1039/d1nr05357d.

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Cerda, María Belén, Milena Batalla, Martina Anton, Eduardo Cafferata, Osvaldo Podhajcer, Christian Plank, Olga Mykhaylyk, and Lucia Policastro. "Enhancement of nucleic acid delivery to hard-to-transfect human colorectal cancer cells by magnetofection at laminin coated substrates and promotion of the endosomal/lysosomal escape." RSC Advances 5, no. 72 (2015): 58345–54. http://dx.doi.org/10.1039/c5ra06562c.

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Optimization of nucleic acid delivery in hard-to-transfect colorectal cancer cells by magnetofection at coated laminin substrates and by the endosomal escape enhancement of magnetic complexes using INF-7 peptide.
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Дисертації з теми "Endosomal escape peptide"

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Lee, I.-Lin. "Non-viral gene delivery systems : incorporation of KALA peptide for endosomal escape." Thesis, University of Nottingham, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.415698.

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2

Lundberg, Pontus. "Naturally derived cell-penetrating peptides and applications in gene regulation : A study on internalization mechanisms and endosomal escape." Doctoral thesis, Stockholm : Dept. of Neurochemistry, Stockholm University, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-1328.

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Ferreira, Vasconcelos Luis Daniel. "Oligonucleotide Complexes with Cell-Penetrating Peptides : Structure, Binding, Translocation and Flux in Lipid Membranes." Licentiate thesis, Stockholms universitet, Institutionen för neurokemi, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-109299.

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The ability of cell-penetrating peptides to cross plasma membranes has been explored for various applications, including the delivery of bioactive molecules to inhibit disease-causing cellular processes. The uptake mechanisms by which cell-penetrating peptides enter cells depend on the conditions, such as the cell line the concentration and the temperature. To be used as therapeutics, each novel cell-penetrating peptide needs to be fully characterized, including their physicochemical properties, their biological activity and their uptake mechanism. Our group has developed a series of highly performing, non-toxic cell-penetrating peptides, all derived from the original sequence of transportan 10. These analogs are called PepFects and NickFects and they are now a diverse family of N-terminally stearylated peptides. These peptides are known to form noncovalent, nano-sized complexes with diverse oligonucleotide cargoes. One bottleneck that limits the use of this technology for gene therapy applications is the efficient release of the internalized complexes from endosomal vesicles. The general purpose of this thesis is to reveal the mechanisms by which our in house designed peptides enter cells and allow the successful transport of biofunctional oligonucleotide cargo. To reach this goal, we used both biophysical and cell biology methods. We used spectroscopy methods, including fluorescence, circular dichroism and dynamic light scattering to reveal the physicochemical properties. Using confocal and transmission electron microscopy we observed and tracked the internalization and intracellular trafficking. Additionally we tested the biological activity in vitro and the cellular toxicity of the delivery systems. We conclude that the transport vectors involved in this study are efficient at perturbing lipid membranes, which correlates with their remarkable capacity to transport oligonucleotides into cells. The improved and distinct capacities to escape from endosomal vesicles can be the result of their different structures and hydrophobicity. These findings extend the knowledge of the variables that condition intracellular Cell-penetrating peptide mediated transport of nucleic acids, which ultimately translates into a small step towards successful non-viral gene therapy.
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4

Qian, Ziqing. "Developments and Applications of Cyclic Cell Penetrating Peptides." The Ohio State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=osu1405340891.

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Cordier, Céline. "Internalisation cellulaire et activité biologique de PNA bloqueurs stériques de la traduction, conjugués au peptide (R/W)9." Phd thesis, Université René Descartes - Paris V, 2014. http://tel.archives-ouvertes.fr/tel-00964872.

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Les Peptide Nucleic Acids (PNA) sont des oligonucléotides antisens analogues de l'ADN, dont le squelette phosphodiester a été remplacé par un squelette pseudo-peptidique d'unités 2-aminoéthylglycine, sur lequel sont greffées des bases azotées. Des PNA dirigés contre les ARN messagers peuvent inhiber la traduction in vitro et dans les cellules humaines. Lorsqu'ils sont dirigés contre la partie codante du transcrit, des PNA polypyrimidiques peuvent bloquer physiquement l'élongation de la traduction en stoppant la machinerie ribosomale. Le transcrit n'est pas dégradé et une protéine tronquée est générée in vitro. Dans le cas de protéines dont la surexpression conduit à des pathologies, des protéines tronquées inactives peuvent jouer un rôle de dominant négatif dans les cellules. Des protéines tronquées de l'Insulin-like Growth Factor-1 (IGF1R), récepteur cellulaire surexprimé dans de nombreux cancers, inhibent la tumorigénèse et la résistance à l'apoptose de cellules cancéreuses. La pénétration cellulaire des PNA est la principale limite à leur utilisation in vivo et il est nécessaire de développer des transporteurs efficaces pour ces oligonucléotides neutres. Les Cell Penetrating Peptides (CPP) sont des peptides naturels ou synthétiques, qui peuvent être conjugués à différentes molécules pour promouvoir leur internalisation cellulaire. Les objectifs de ce travail de thèse étaient de comprendre les critères requis pour l'arrêt de l'élongation de la traduction par les PNA et d'étudier leur internalisation cellulaire médiée par le CPP (R/W)9. Nous avons montré qu'un couplage covalent entre ce peptide et deux PNA 13-mer permet l'internalisation des conjugués dans un système cellulaire rapporteur, conduisant à leur activité biologique en présence d'un agent lysosomotropique. Les conjugués interagissent avec les glycosaminoglycanes membranaires et sont internalisés par endocytose en moins d'une heure. De plus, les conjugués formés avec un peptide analogue comportant des lysines sont six fois moins internalisés, mettant en évidence l'importance des résidus arginines du peptide (R/W)9 pour l'interaction avec la membrane. Enfin, nous avons montré que le peptide (R/W)9 couplé à un PNA dirigé contre la séquence codante de l'IGF1R permet son internalisation dans les cellules de cancer de la prostate et que le conjugué inhibe spécifiquement l'expression de la chaîne β du récepteur.
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Arafiles, Jan Vincent Valenzuela. "Macropinocytosis-Inducing Peptides: Identification, Utility, and Mechanism-of-Action." Kyoto University, 2020. http://hdl.handle.net/2433/259021.

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Madani, Fatemeh. "Biophysical studies of peptides with functions in biotechnology and biology." Doctoral thesis, Stockholms universitet, Institutionen för biokemi och biofysik, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-66948.

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My thesis concerns spectroscopic studies (NMR, CD and fluorescence) of peptides with functions in biotechnology and biology, and their interactions with a model membrane (large unilamellar phospholipid vesicles). The resorufin-based arsenical hairpin binder (ReAsH) bound to a short peptide is a useful fluorescent tag for genetic labeling of proteins in living cells. A hairpin structure with some resemblance to type II β-turn was determined by NMR structure calculations (Paper I). Cell-penetrating peptides (CPPs) are short (30-35 residues), often rich in basic amino acids such as Arg. They can pass through the cell membrane and deliver bioactive cargoes, making them useful for biotechnical and pharmacological applications. The mechanisms of cellular uptake and membrane translocation are under debate. Understanding the mechanistic aspects of CPPs is the major focus of Papers II, III, and IV. The effect of the pyrenebutyrate (PB) on the cellular uptake, membrane translocation and perturbation of several CPPs from different subgroups was investigated (Paper II). We concluded that both charge and hydrophobicity of the CPP affect the cellular uptake and membrane translocation efficiency. Endosomal escape is a crucial challenge for the CPP applications. We modeled the endosome and endosomal escape for different CPPs to investigate the corresponding molecular mechanisms (Papers III and IV). Hydrophobic CPPs were able to translocate across the model membrane in the presence of a pH gradient, produced by bacteriorhodopsin proton pumping, whereas a smaller effect was observed for hydrophilic CPPs. Dynorphin A (Dyn A) peptide mutations are associated with neurodegenerative disorders, without involvement of the opioid receptors. The non-opioid activities of Dyn A may involve membrane perturbations. Model membrane-perturbations by three Dyn A mutants were investigated (Paper V). The results showed effects to different degrees largely in accordance with their neurotoxic effects.

At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 4: Manuscript.

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Broad, Amaalia. "A Role for ETA(253-412) in Peptide-based Delivery of Therapeutic Molecules into Cells." Thesis, 2009. http://hdl.handle.net/1807/18890.

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The delivery of biomolecules by cell penetrating peptides (CPPs) is an innovative therapeutic strategy. However delivery efficiency is hindered by the entrapment of CPPs in vesicles, degradation, or recycling out of cells, which limits their delivery into the cell cytoplasm and nucleus. To overcome these barriers, we investigated a bacterial protein domain derived from Pseudomonas aeruginosa, Exotoxin A (ETA, residues 253-412) that is able to exit vesicular compartments. A series of CPP-ETA(253-412) fusion proteins were constructed, expressed, and purified. Confocal microscopy and flow cytometry confirmed the internalization at 37oC of constructs containing CPPs (poly-arginine or TAT). In addition, constructs containing CPP-ETA(253-412)-eGFP were shown to relocate from endosomes to the cytosol. CPP-ETA(253-412) constructs were also able to act as carriers of DNA cargos facilitating their delivery to the cytosol. The ETA(253-412) translocation domain may prove useful for the intracellular delivery of drugs, protein therapeutics, siRNA delivery, and vaccine formulations.
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Číhařová, Barbora. "Studium účinku modifikace virových částic polyhistidinem na jejich intracelulární lokalizaci a dopravu genů do jádra." Master's thesis, 2021. http://www.nusl.cz/ntk/nusl-446452.

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Viral vectors derived from mouse polyomavirus are a convenient tool for studying the targeted delivery of therapeutical agents into the cells and cellular organelles. Vectors derived from mouse polyomavirus face difficulties similar to other nanoparticles, as they often end up trapped inside an endosome where they are subsequently degraded. This diploma explored the potential of vector modifications, which have the potential to make the transport to the nucleus or cytosol more effective. This work had particularly focused on increasing the transduction efficiency by modifying particle's internally localized VP3 capsid protein with covalently bound membrane-penetrating peptides. Primary covalent genetic modification to the VP3 protein was the polyhistidine peptide KH27K. Its potential of improving the transduction effectivity was compared with two other peptide modifications - LAH4 and R8. The results of the transduction test showed that covalently bound R8 peptide had many-fold improved the transport to the nucleus when compared to the unmodified particles. The modification with LAH4 peptide had been regarded more effective only when was associated with the particles non-covalently. In such scenario the transduction efficiency rose 40-times when compared with unmodified particles. Polyhistidine...
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Частини книг з теми "Endosomal escape peptide"

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de Schutter, Kristof, Olivier Christiaens, Clauvis Nji Tizi Taning, and Guy Smagghe. "Boosting dsRNA delivery in plant and insect cells with peptide- and polymer-based carriers: case-based current status and future perspectives." In RNAi for plant improvement and protection, 102–16. Wallingford: CABI, 2021. http://dx.doi.org/10.1079/9781789248890.0011.

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Abstract Since the discovery of this naturally occurring endogenous regulatory and defence mechanism, RNA interference (RNAi) has been exploited as a powerful tool for functional genomic research. In addition, it has evolved as a promising candidate for a sustainable, specific and ecofriendly strategy for pest management and plant improvement. A key element in this technology is the efficient delivery of dsRNAs into the pest or plant tissues. While several examples using transgenic plants expressing the dsRNAs have proved the potential of this technology, nontransgenic approaches are investigated as alternatives, allowing flexibility and circumventing technical limitations of the transgenic approach. However, the efficacy of environmental RNAi is affected by several barriers, such as extracellular degradation of the dsRNA, inefficient internalization of the dsRNA in the cell and low endosomal escape into the cytoplasm, resulting in variable or low RNAi responses. In the medical field, carrier systems are commonly used to enhance RNA delivery and these systems are being rapidly adopted by the agricultural industry. Using four case studies, this chapter demonstrates the potential of carriers to improve the RNAi response in pest control for aquatic-living mosquito larvae and RNAi-resilient Lepidoptera and to cross the plant cell wall, allowing efficient environmental RNAi in plants.
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2

de Schutter, Kristof, Olivier Christiaens, Clauvis Nji Tizi Taning, and Guy Smagghe. "Boosting dsRNA delivery in plant and insect cells with peptide- and polymer-based carriers: case-based current status and future perspectives." In RNAi for plant improvement and protection, 102–16. Wallingford: CABI, 2021. http://dx.doi.org/10.1079/9781789248890.0102.

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Анотація:
Abstract Since the discovery of this naturally occurring endogenous regulatory and defence mechanism, RNA interference (RNAi) has been exploited as a powerful tool for functional genomic research. In addition, it has evolved as a promising candidate for a sustainable, specific and ecofriendly strategy for pest management and plant improvement. A key element in this technology is the efficient delivery of dsRNAs into the pest or plant tissues. While several examples using transgenic plants expressing the dsRNAs have proved the potential of this technology, nontransgenic approaches are investigated as alternatives, allowing flexibility and circumventing technical limitations of the transgenic approach. However, the efficacy of environmental RNAi is affected by several barriers, such as extracellular degradation of the dsRNA, inefficient internalization of the dsRNA in the cell and low endosomal escape into the cytoplasm, resulting in variable or low RNAi responses. In the medical field, carrier systems are commonly used to enhance RNA delivery and these systems are being rapidly adopted by the agricultural industry. Using four case studies, this chapter demonstrates the potential of carriers to improve the RNAi response in pest control for aquatic-living mosquito larvae and RNAi-resilient Lepidoptera and to cross the plant cell wall, allowing efficient environmental RNAi in plants.
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